3D Encapsulation, Bioprinting and Controlled Delivery of Functionally Engineered EVs (FEEs)

功能工程电动汽车 (FEE) 的 3D 封装、生物打印和受控交付

• 批准号: 10433850
• 负责人: LYNDON F COOPER
• 金额: $ 46.22万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-18 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10433850
• 关键词: 3-Dimensional; 3D Print; Activities of Daily Living; Address; Alginates; Anti-Inflammatory Agents; Architecture; Area; BMP2 gene; Binding; Biological Assay; Biological Models; Biology; Calvaria; Cartilage; Cells; Chronic; Complex; Cues; Defect; Dental; Development; Disease; Dose; Encapsulated; Engineering; Equilibrium; Event; Extracellular Matrix; Genes; Goals; Growth Factor; Health; Histology; Hybrids; Hydrogels; Immunology; Impairment; Individual; Inflammasome; Inflammation; Inflammatory; Injury; Ink; Kinetics; Knowledge; Laboratories; MADH7 gene; MMP2 gene; Measurement; Mediator of activation protein; Mesenchymal Stem Cells; MicroRNAs; Modeling; Muscle; Musculoskeletal; Musculoskeletal System; Natural regeneration; Nerve; Pathway interactions; Peptides; Play; Polymers; Process; Production; Property; Rattus; Regenerative Medicine; Regenerative pathway; Reporter; Role; Signal Transduction; Site; Structure; System; Techniques; Technology; Testing; Therapeutic; Time; Tissues; Work; base; bioprinting; body system; clinical translation; controlled release; craniofacial; craniofacial tissue; crosslink; cytokine; extracellular vesicles; immunoregulation; improved; in vivo; macrophage; monomer; novel strategies; paracrine; precision medicine; prevent; protein expression; recruit; regenerative; repaired; scaffold; spatiotemporal; stem cell exosomes; stem cell growth; stem cell therapy; tissue injury; tissue regeneration; tissue repair; tool

Summary: Tissue repair is a complex process that involves a delicate temporal balance between inflammatory and regenerative mechanisms. In health, initial inflammatory events are replaced by regenerative processes in a coordinated manner. This sequence is disrupted in diseased states and complex injuries. The goal of regenerative medicine is to reestablish this balance by preventing chronic/aberrant inflammation and promoting repair and regeneration in a tissue-specific manner. While stem cell and growth factor therapies have been explored for this purpose traditionally, recent studies highlight the immunomodulatory and protective functions of mesenchymal stem cell derived extracellular vesicles (MSC EVs). Although MSC EVs possess versatile properties, to engage tissue-specific pathways and fit the goals of precision medicine with translational relevance, MSC EVs have to be engineered for enhanced pathway-specific functionality and delivered on site in a spatially and temporally controlled manner. In this proposal, leveraging our preliminary results and our expertise in EV biology, immunology and bone biology, we hypothesize that: Spatiotemporal control of immunomodulatory and regenerative pathways can be achieved by selective incorporation of Functionally Engineered EVs (FEEs)in 3D printed scaffolds. Using bone regeneration as a model system, we will test this hypothesis in three specific aims. In aim 1, we will generate functionally engineered EVs (FEEs) that target specific osteoinductive and immunomodulatory pathways. In aim 2, we will develop a photocrosslinkable alginate-based delivery system with EV carrier and release motifs for spatial localization and temporally controlled delivery of the FEEs developed in aim 1. In aim 3, we will utilize 3D printing technology to print defined structures encapsulating the FEEs for spatially and temporally controlled biphasic delivery in vivo. This system will be tested in a rat calvarial defect model. From the proposed studies, we will develop a platform technology that can impact the field of regenerative medicine beyond the craniofacial and musculoskeletal systems.

总结： 组织修复是一个复杂的过程，涉及炎症和炎症反应之间微妙的时间平衡。 再生机制在健康状况下，最初的炎症事件被再生过程所取代， 协调的方式。这种顺序在疾病状态和复杂损伤中被破坏。的目标 再生医学是通过预防慢性/异常炎症和促进 以组织特异性方式修复和再生。虽然干细胞和生长因子疗法已经被广泛应用， 传统上，人们一直在探索这一目的，最近的研究强调了免疫调节和保护功能， 间充质干细胞衍生的细胞外囊泡（MSC EV）。虽然MSC EV拥有多功能 属性，从事组织特异性途径，并符合精准医学的目标与翻译 相关性，MSC EV必须被设计用于增强特定于路径的功能并在现场交付 以空间和时间受控的方式。在本提案中，利用我们的初步结果和我们的 凭借EV生物学、免疫学和骨生物学的专业知识，我们假设：时空控制 免疫调节和再生途径可以通过选择性地掺入功能性的 3D打印支架中的工程电动汽车（FEE）。使用骨再生作为模型系统，我们将测试这一点 三个具体目标。在目标1中，我们将产生功能性工程电动汽车（FEE）， 特异性骨诱导和免疫调节途径。在aim 2中，我们将开发一种可光致交联的 具有EV载体和释放基序的基于藻酸盐的递送系统， 目标1中制定的FEE的控制下交付。在目标3中，我们将利用3D打印技术打印 限定的结构封装FEE，用于在体内进行空间和时间上受控的双相递送。这 系统将在大鼠颅骨缺损模型中进行测试。根据拟议的研究，我们将开发一个平台， 技术，可以影响再生医学领域超越颅面和肌肉骨骼 系统.